Monoclonal antibodies against endotrophin and the use thereof

Abstract

Aspects of the present invention relate to methods and reagents for increasing chemosensitivity to platinum-based chemotherapy. In one aspect, a method of increasing chemosensitivity to platinum-based chemotherapy is provided, comprising administering to a patient in need thereof an effective amount of an endotrophin-neutralizing agent. The agent can be a monoclonal antibody, or fragment thereof, capable of binding to the C5 domain of the alphas chain of collagen VI. In some embodiments, the method can further include administering an effective amount of thiazolidinedione to said patient.

What is claimed is: 
     
       1. A monoclonal antibody or an antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof comprises HCDR1, HCDR2, and HCDR3 amino acid sequences provided in a heavy chain variable domain (VH) amino acid sequence of SEQ ID NO: 157 and LCDR1, LCDR2, and LCDR3 amino acid sequences provided in a light chain variable domain (VL) amino acid sequence of SEQ ID NO: 158. 
     
     
       2. The monoclonal antibody or antigen binding fragment thereof of  claim 1 , wherein the HCDR1, HCDR2, and HCDR3 comprise the amino acid sequences of SEQ ID NOs: 52, 53, and 54, respectively. 
     
     
       3. The monoclonal antibody or antigen binding fragment thereof of  claim 1 , wherein the LCDR1, LCDR2, and LCDR3 comprise the amino acid sequences of SEQ ID NOs: 7, 8, and 9, respectively. 
     
     
       4. The monoclonal antibody or antigen binding fragment thereof of  claim 1 , wherein the antibody or an antigen binding fragment thereof comprises a VH comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 157. 
     
     
       5. The monoclonal antibody or antigen binding fragment thereof of  claim 1 , wherein the antibody or an antigen binding fragment thereof comprises a VL comprising an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 158. 
     
     
       6. The monoclonal antibody or antigen binding fragment thereof of  claim 4 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 157. 
     
     
       7. The monoclonal antibody or antigen binding fragment thereof of  claim 5 , wherein the VL comprises the amino acid sequence of SEQ ID NO: 158. 
     
     
       8. The monoclonal antibody or antigen binding fragment thereof of  claim 1 , wherein the antibody or an antigen binding fragment thereof comprises a VH and a VL, wherein the VH comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 157 and the VL comprises an amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 158. 
     
     
       9. The monoclonal antibody or antigen binding fragment thereof of  claim 8 , wherein the VH comprises the amino acid sequence of SEQ ID NO: 157 and the VL comprises the amino acid sequence of SEQ ID NO: 158. 
     
     
       10. The monoclonal antibody or antigen binding fragment thereof of  claim 1 , wherein the antibody or antigen binding fragment thereof is a humanized antibody. 
     
     
       11. The monoclonal antibody or antigen binding fragment thereof of  claim 1 , wherein the antibody fragment is a monovalent scFv (single chain fragment variable) antibody, divalent scFv, Fab fragment, F(ab′) 2  fragment, F(ab′) 3  fragment, Fv fragment, or single chain antibody. 
     
     
       12. The monoclonal antibody or antigen binding fragment thereof of  claim 1 , wherein the antibody is a chimeric antibody or bispecific antibody. 
     
     
       13. The monoclonal antibody or antigen binding fragment thereof of  claim 1 , wherein the antibody is an IgG antibody or antigen binding fragment thereof or a recombinant IgG antibody or antigen binding fragment thereof. 
     
     
       14. The monoclonal antibody or antigen binding fragment thereof of  claim 1 , wherein the antibody is conjugated or fused to an imaging agent or a cytotoxic agent.